InterPro domain: IPR015813

Pyruvate kinase controls the exit from the glysolysis pathway, catalysing the transfer of phosphate from phosphooenolpyruvate (PEP) to ADP. Mammalian pyruvate kinase is a homotetramer, where each polypeptide subunit consists of four domains: N-terminal, A domain, B domain and C-terminal. Activation of the enzyme is believed to occur via the clamping down of the B domain onto the A domain to dehydrate the active site cleft. The N- and C-terminal domains are situated at inter-subunit contact sites, and could be involved in assembly and communication within the complex. The N-terminal domain has a TIM beta/alpha-barrel structure. Homologous TIM-barrel domains are found in the following proteins:

• N-terminal of pyruvate kinase ( 2.7.1.40 ), which is interrupted by an all-beta domain [ 1 ].
• C-terminal of pyruvate phosphate dikinase ( 2.7.9.1 ), which has a similar mode of substrate binding to pyruvate kinase [ 2 ].
• Phosphoenolpyruvate carboxylase ( 4.1.1.31 ); this domain has additional helices [ 3 ].
• Phosphenolpyruvate mutase( 5.4.2.9 )/Isocitrate lyase ( 4.1.3.1 ), where it forms a swapped dimer [ 4 ].
• HpcH/HpaI aldolases, such as the beta subunit of citrate lyase, where it forms a swapped dimer, and contains a pyruvate kinase-type metal binding site [ 5 ].
• Ketopantoate hydroxymethyltransferase PanB ( 2.1.2.11 ), where a C-terminal helix exchange is observed in some enzymes [ 6 ].

1. Structural and functional linkages between subunit interfaces in mammalian pyruvate kinase. J. Mol. Biol. 312, 525-40
2. Pyruvate site of pyruvate phosphate dikinase: crystal structure of the enzyme-phosphonopyruvate complex, and mutant analysis. Biochemistry 41, 780-7
3. Crystal structures of C4 form maize and quaternary complex of E. coli phosphoenolpyruvate carboxylases. Structure 10, 1721-30
4. The structure and domain organization of Escherichia coli isocitrate lyase. Acta Crystallogr. D Biol. Crystallogr. 57, 1209-18
5. Electron microscopic studies on retinochoroidal atrophy in the human eye. Acta Med. Okayama 36, 11-21
6. Structure of E. coli ketopantoate hydroxymethyl transferase complexed with ketopantoate and Mg2+, solved by locating 160 selenomethionine sites. Structure 11, 985-96